The long-term objective of this research program is to better understand the mechanisms of action of treatments that target the cortical modulation of chronic pain. Evidence indicates that the brain is not a passive recipient of painful (nociceptive) information, but actively processes and modulates that information at many levels, including at the level of the cortex. Preliminary evidence suggests that a number of interventions that target cortical activity may reduce pain experience because they produce relative increases in slower wave (alpha) cortical activity and relative decreases in faster wave (beta) cortical activity, although these hypothesized effects on cortical activity have not yet been directly tested. The proposed study will test and compare the impact of three innovative neuromodulatory approaches (neurofeedback, self-hypnosis training, and transcranial direct current stimulation) on both pain intensity and on cortical brain activity, as indexed by EEG, in a sample of persons with spinal cord injury and refractory chronic neuropathic (n=25) or musculoskeletal (n=25) pain. 50 study participants will be given a single session of all three active treatments, a placebo (sham) transcranial direct current stimulation intervention, and a meditation intervention. The treatment sessions will be separated by at least one week, and both EEG-assessed cortical activity and pain intensity will be assessed before and after each session. Analyses will test the hypotheses that: (1) each active treatment reduces perceived pain more than the control treatments, (2) each active treatment increases relative alpha wave and decreases relative beta wave EEG-assessed cortical activity, and (3) the effects of the active treatments on pain are mediated by their impact on cortical activity. The results from study will allow us to understand the relative effects of three procedures that are thought to decrease pain by modulating cortical activity. The data will also help us understand which of these procedures warrant further investigation for the management of chronic pain, and the potential utility of using EEG-assessed cortical activity as a means of understanding and measuring the effects of these and other treatments. Ultimately, the information from this study could contribute to the development and testing of more effective interventions for the management of refractory chronic pain. For these reasons, the proposal is consistent with the goals of the R21 funding mechanism. That is, it is a study that assesses "...the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research." (National Institutes of Health, 2008). PUBLIC HEALTH RELEVANCE: Chronic pain is a significant public health problem, and many people suffer from severe chronic pain that cannot be adequately managed with the treatments that are currently available. We now understand that chronic pain can be influenced by treatments that alter how the brain processes pain information. This research program will help us better understand the effects of these treatments on brain activity, and this information will help guide us in the development of new effective treatments for chronic pain.